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Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein

Abstract

PrPc is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPc. Mice homozygous for disrupted PrP genes have been generated. Surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. It is now feasible to determine whether mice devoid of PrPc can propagate prions and are susceptible to scrapie pathogenesis.

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References

  1. Prusiner, S. B. Science 252, 1515–1522 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Prusiner, S. B. Science 216, 136–144 (1982).

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Hsiao, K. & Prusiner, S. B. Neurology 40, 1820–1827 (1990).

    Article  CAS  PubMed  Google Scholar 

  4. Diringer, H. et al. Nature 306, 476–478 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. McKinley, M. P., Bolton, D. C. & Prusiner, S. B. Cell 35, 57–62 (1983).

    Article  CAS  PubMed  Google Scholar 

  6. Hope, J. et al. EMBO J. 5, 2591–2597 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gabizon, R., McKinley, M. P., Groth, D. & Prusiner, S. B. Proc. natn. Acad. Sci. U.S.A. 85, 6617–6621 (1988).

    Article  ADS  CAS  Google Scholar 

  8. Dickinson A. G., Meikle, V. M. & Fraser, H. J. comp. Pathol. 78, 293–299 (1968).

    Article  CAS  PubMed  Google Scholar 

  9. Dickinson, A. G. & Meikle, V. M. Molec. gen. Genet. 112, 73–79 (1971).

    Article  CAS  PubMed  Google Scholar 

  10. Carlson, G. A. et al. Cell 46, 503–511 (1986).

    Article  CAS  PubMed  Google Scholar 

  11. Hunter, N., Hope, J., McConnell, I. & Dickinson, A. G. J. gen. Virol. 68, 2711–2716 (1987).

    Article  CAS  PubMed  Google Scholar 

  12. Carlson, G. A., Westaway, D., DeArmond, S. J., Peterson Torchia, M. & Prusiner, S. B. Proc. natn. Acad. Sci. U.S.A. 86, 7475–7479 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Race, R. E., Graham, K., Ernst, D., Caughey, B. & Chesebro, B. J. gen. Virol. 71, 493–497 (1990).

    Article  CAS  PubMed  Google Scholar 

  14. Hsiao, K. et al. Nature 338, 342–345 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Hsiao, K. K. et al. Science 250, 1587–1590 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  16. Harris, D. A., Falls, D. L., Johnson, F. A. & Fischbach, G. D. Proc. natn. Acad. Sci. U.S.A. 88, 7664–7668 (1991).

    Article  ADS  CAS  Google Scholar 

  17. Basler, K. et al. Cell 46, 417–428 (1986).

    Article  CAS  PubMed  Google Scholar 

  18. Locht, C., Chesebro, B., Race, R. & Keith, J. M. Proc. natn. Acad. Sci. U.S.A. 83, 6372–6376 (1986).

    Article  ADS  CAS  Google Scholar 

  19. KretzsChmar, H. A. et al. DNA 5, 315–324 (1986).

    Article  CAS  PubMed  Google Scholar 

  20. Puckett, C., Concannon, P., Casey, C. & Hood, L. Am. J. hum. Genet. 49, 320–329 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Westaway, D. & Prusiner, S. B. Nucleic Acids Res. 14, 2035–2044 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Goldmann, W., Hunter, N., Martin, T., Dawson, M. & Hope, J. J. gen. Virol. 72, 201–204 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. Kretzschmar, H. A., Prusiner, S. B., Stowring, L. E. & DeArmond, S. J. Am. J. Path. 122, 1–5 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Cashman, N. R. et al. Cell 61, 185–192 (1990).

    Article  CAS  PubMed  Google Scholar 

  25. Caughey, B., Race, R. E., Ernst, D., Buchmeier, M. J. & Chesebro, B. J. Virol. 63, 175–181 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Borchelt, D. R., Scott, M., Taraboulos, A., Stahl, N. & Prusiner, S. B. J. Cell Biol. 110, 743–752 (1990).

    Article  CAS  PubMed  Google Scholar 

  27. Manson, J. et al. Development (in the press).

  28. Doetschman, T. et al. Nature 330, 576–578 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Thomas, K. R. & Capecchi, M. R. Cell 51, 503–512 (1987).

    Article  CAS  PubMed  Google Scholar 

  30. Capecchi, M. R. Trends. Genet. 5, 70–76 (1989).

    Article  CAS  PubMed  Google Scholar 

  31. McMahon, A. P. & Bradley, A. Cell 62, 1073–1085 (1990).

    Article  CAS  PubMed  Google Scholar 

  32. Thomas, L. J. et al. J. biol. Chem. 266, 23175–23184 (1991).

    CAS  PubMed  Google Scholar 

  33. Stahl, N., Borchelt, D. R., Hsiao, K. & Prusiner, S. B. Cell 51, 229–240 (1987).

    Article  CAS  PubMed  Google Scholar 

  34. DeArmond, S. J. et al. Neurology 37, 1271–1280 (1987).

    Article  CAS  PubMed  Google Scholar 

  35. Morris, R. G. M. J. Neurosci. Meth. 11, 47–60 (1984).

    Article  CAS  Google Scholar 

  36. Morris, R. G. M., Garrud, P., Rawlins, J. N. P. & O'Keefe, J. Nature 297, 681–683 (1982).

    Article  ADS  CAS  PubMed  Google Scholar 

  37. Schöpke, R., Wolfer, D. P., Lipp, H.-P. & Leisinger-Trigona, M.-C. Hippocampus 1, 315–328 (1991).

    Article  PubMed  Google Scholar 

  38. Wehner, J. M., Sleight, S. & Upchurch, M. Brain Res. 523, 181–187 (1990).

    Article  CAS  PubMed  Google Scholar 

  39. Lipp, H.-P. & Van der Loos, H. Behavl Brain Res. 45, 135–145 (1991).

    Article  CAS  Google Scholar 

  40. Anisman, H. in The Psychopharmacology of Aversively Motivated Behavior (eds Anisman, H. & Bignami, G.) 1–62 (Plenum, New York, 1978).

    Google Scholar 

  41. Lipp, H. P., Schwegler, H., Heimrich, B. & Driscoll, P. J. Neurosci. 8, 1905–1921 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Oesch, B. et al. Cell 40, 735–746 (1985).

    Article  CAS  PubMed  Google Scholar 

  43. Butler, D. A. et al. J. Virol. 62, 1558–1564 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Taraboulos, A., Serban, D. & Prusiner, S. B. J. Cell Biol. 110, 2117–2132 (1990).

    Article  CAS  PubMed  Google Scholar 

  45. McKinley, M. P. et al. J. Cell Biol. 111, 316a (1990).

    Google Scholar 

  46. Scott, M. et al. Cell 59, 847–857 (1989).

    Article  CAS  PubMed  Google Scholar 

  47. Prusiner, S. B. et al. Cell 63, 673–686 (1990).

    Article  CAS  PubMed  Google Scholar 

  48. Westaway, D. et al. Neuron 7, 59–68 (1991).

    Article  CAS  PubMed  Google Scholar 

  49. Nagase, S., Shimamune, K. & Shumiya, S. Science 205, 590–591 (1979).

    Article  ADS  CAS  PubMed  Google Scholar 

  50. Goebl, M. G. & Petes, T. D. Cell 46, 983–992 (1986).

    Article  CAS  PubMed  Google Scholar 

  51. Ferguson, E. L. & Horvitz, H. R. Genetics 123, 109–121 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Elklns, T., Zinn, K., McAllister, L., Hoffmann, F. M. & Goodman, C. S. Cell 60, 565–575 (1990).

    Article  Google Scholar 

  53. Hooper, M. L., Hardy, K., Handyside, A., Hunter, S. & Monk, M. Nature 326, 292–295 (1987).

    Article  ADS  CAS  PubMed  Google Scholar 

  54. Zijlstra, M. et al. Nature 344, 742–746 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  55. Zijlstra, M., Li, E., Sajjadik, F., Subramani, S. & Jaenisch, R. Nature 342, 435–438 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  56. Koller, B. H., Marrack, P., Kappler, J. W. & Smithies, O. Science 248, 1227–1230 (1990).

    Article  ADS  CAS  PubMed  Google Scholar 

  57. Schorle, H., Holtschke, T., Hunig, T., Schimpl, A. & Horak, I. Nature 352, 621–624 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  58. Joyner, A. L., Herrup, K., Auerbach, B. A., Davis, C. A. & Rossant, J. Science 251, 1239–1243 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  59. Westaway, D. et al. Cell 51, 651–662 (1987).

    Article  CAS  PubMed  Google Scholar 

  60. Saiki, R. K. et al. Science 239, 487–491 (1988).

    Article  ADS  CAS  PubMed  Google Scholar 

  61. Bradley, A. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach (ed. Robertson, E. J.) 113–151 (IRL, Oxford, 1987).

    Google Scholar 

  62. Hogan, B. Costantini, F. & Lacy, E. Manipulating the Mouse Embryo: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1986).

    Google Scholar 

  63. Church, G. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).

    Article  ADS  CAS  Google Scholar 

  64. Serban, D., Taraboulos, A., DeArmond, S. J. & Prusiner, S. B. Neurology 40, 110–117 (1990).

    Article  CAS  PubMed  Google Scholar 

  65. Auffray, C. & Rougeon, F. Eur. J. Biochem. 107, 303–314 (1980).

    Article  CAS  PubMed  Google Scholar 

  66. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1989).

    Google Scholar 

  67. Lämmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  Google Scholar 

  68. Siegel, S. Nonparametric Statistics for the Behavioral Sciences (MacGraw Hill, London, 1956).

    MATH  Google Scholar 

  69. Wolfer, D. P. & Lipp, H.-P. J. Neurosci. Meth. 41, 65–74 (1992).

    Article  CAS  Google Scholar 

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Büeler, H., Fischer, M., Lang, Y. et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356, 577–582 (1992). https://doi.org/10.1038/356577a0

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